"Peripheral Mechanisms of Deafness" proposes to test the hypothesis that normal cochlear mechanics are dependent on active (energy- consuming) processes which functionally feed back onto the vibration of the basilar membrane. Specifically, this project will attempt to establish whether the outer hair cell of the mammalian inner ear participate in determining the properties of the basilar membrane, thus also largely determining the response properties of the cochlear primary afferents. Two parallel strategies, both based on the disruption of the normal function of the organ of Corti, will be used. The first strategy consists of measuring the acoustically-evoked vibrations of the basilar membrane before, during and after transient (reversible) alterations or dysfunction of the outer hair cells, induced by procedures such as stimulation of the olivocochlear efferent system, injection of diuretics or instillation of cyanide into the perilymphatic spaces. The second strategy consists of studying the activity of individual cochlear afferents in animals whose cochleas have been permanently damaged by chronic administration of ototoxic agents. Both sets of measurements, mechanical on the basilar membrane and microelectrode recordings from cochlear afferents, will be performed in a single species, the chinchilla. The basilar membrane vibration will be measured by means of an application of the Mossbauer effect that permits detection of very low velocities (e.g., 0.03 mm/sec). Results of the proposed investigation will be of value in defining the bidirectional relationship between the sensory hair cells and the basilar membrane in normal mammalian cochleas and will also serve to clarify the pathophysiology of sensorineural hearing loss in humans.